RESUMO
OBJECTIVE: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. METHODS: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures included the mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. RESULTS: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. CONCLUSIONS: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Conjuntivite/epidemiologia , Dermatite Atópica/tratamento farmacológico , Reação no Local da Injeção/epidemiologia , Prurido/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Conjuntivite/induzido quimicamente , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Esquema de Medicação , Feminino , Humanos , Reação no Local da Injeção/etiologia , Injeções Subcutâneas , Masculino , Prurido/diagnóstico , Prurido/imunologia , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Atopic dermatitis (AD) is a common skin disease characterized by chronic inflammation and itchiness. Although skin barrier dysfunction and immune abnormalities are thought to contribute to the development of AD, the precise pathogenic mechanism remains to be elucidated. We have developed a unique, diet-induced AD mouse model based on the findings that deficiencies of certain polyunsaturated fatty acids and starches cause AD-like symptoms in hairless mice. Here, we present a protocol and tips for establishing an AD mouse model using a custom diet modified from a widely used standard diet (AIN-76A Rodent Diet). We also describe methods for evaluating skin barrier dysfunction and analyzing itch-related scratching behavior. This model can be used not only to investigate the complex pathogenic mechanism of human AD but also to study the puzzling relationship between nutrition and AD development.
Assuntos
Dermatite Atópica/imunologia , Modelos Animais de Doenças , Ácidos Graxos Insaturados/química , Alimentos Formulados , Prurido/imunologia , Amido/química , Animais , Comportamento Animal , Óleo de Milho/química , Dermatite Atópica/etiologia , Dermatite Atópica/fisiopatologia , Etanol/química , Ácidos Graxos Insaturados/deficiência , Ácidos Graxos Insaturados/imunologia , Feminino , Humanos , Camundongos , Camundongos Pelados , Permeabilidade , Prurido/etiologia , Prurido/fisiopatologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Amido/deficiência , Amido/imunologiaRESUMO
Rationale: Psoriasis is a chronic inflammatory disease caused by a complex interplay between the immune and nervous systems with recurrent scaly skin plaques, thickened stratum corneum, infiltration and activation of inflammatory cells, and itch. Despite an increasing availability of immune therapies, they often have adverse effects, high costs, and dissociated effects on inflammation and itch. Activation of sensory neurons innervating the skin and TRPV1 (transient receptor potential vanilloid 1) are emerging as critical components in the pathogenesis of psoriasis, but little is known about their endogenous inhibitors. Recent studies have demonstrated that resolvins, endogenous lipid mediators derived from omega-3 fatty acids, are potent inhibitors of TRP channels and may offer new therapies for psoriasis without known adverse effects. Methods: We used behavioral, electrophysiological and biochemical approaches to investigate the therapeutic effects of resolvin D3 (RvD3), a novel family member of resolvins, in a preclinical model of psoriasis consisting of repeated topical applications of imiquimod (IMQ) to murine skin, which provokes inflammatory lesions that resemble human psoriasis. Results: We report that RvD3 specifically reduced TRPV1-dependent acute pain and itch in mice. Mechanistically, RvD3 inhibited capsaicin-induced TRPV1 currents in dissociated dorsal root ganglion (DRG) neurons via the N-formyl peptide receptor 2 (i.e. ALX/FPR2), a G-protein coupled receptor. Single systemic administration of RvD3 (2.8 mg/kg) reversed itch after IMQ, and repeated administration largely prevented the development of both psoriasiform itch and skin inflammation with concomitant decreased in calcitonin gene-related peptide (CGRP) expression in DRG neurons. Accordingly, specific knockdown of CGRP in DRG was sufficient to prevent both psoriasiform itch and skin inflammation similar to the effects following RvD3 administration. Finally, we elevated the translational potential of this study by showing that RvD3 significantly inhibited capsaicin-induced TRPV1 activity and CGRP release in human DRG neurons. Conclusions: Our findings demonstrate a novel role for RvD3 in regulating TRPV1/CGRP in mouse and human DRG neurons and identify RvD3 and its neuronal pathways as novel therapeutic targets to treat psoriasis.
Assuntos
Ácidos Graxos Insaturados/farmacologia , Dor/tratamento farmacológico , Prurido/tratamento farmacológico , Psoríase/tratamento farmacológico , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Biópsia , Peptídeo Relacionado com Gene de Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/toxicidade , Células Cultivadas , Modelos Animais de Doenças , Ácidos Graxos Insaturados/uso terapêutico , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/imunologia , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Neuroimunomodulação/efeitos dos fármacos , Neuroimunomodulação/imunologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Dor/induzido quimicamente , Dor/imunologia , Dor/patologia , Técnicas de Patch-Clamp , Cultura Primária de Células , Prurido/induzido quimicamente , Prurido/imunologia , Prurido/patologia , Psoríase/complicações , Psoríase/imunologia , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/inervação , Canais de Cátion TRPV/metabolismoRESUMO
Primary biliary cholangitis is a cholestatic, chronic autoimmune liver disease with a wide individual variation in disease progression. The diagnosis is predominantly based on chronic elevation of alkaline phosphatase and the presence of anti-mitochondrial antibodies or other specific antinuclear antibodies (i.e. anti-gp210 and anti-sp100). Even in early-stage disease, health-related quality of life can be severely impaired by symptoms such as pruritus, fatigue, and sicca syndrome and metabolic bone disease should be assessed and treated. The prognosis of the disease is, however, largely determined by the development of cirrhosis and its complications. Ursodeoxycholic acid is associated with an improved prognosis and should be initiated and continued in all patients. Clinical outcome is related to the biochemical response to ursodeoxycholic acid, but the prognosis of those with an incomplete response is still better than those who remain untreated. Obeticholic acid was recently approved as second-line treatment and bezafibrate may serve as an adequate off-label alternative, particularly in patients with pruritus. Preliminary data suggest an additive effect of triple therapy with ursodeoxycholic acid, obeticholic acid, and bezafibrate, whereas other promising drugs are being evaluated in clinical trials.
Assuntos
Doenças Autoimunes/diagnóstico , Colagogos e Coleréticos/uso terapêutico , Doença Hepática Terminal/terapia , Cirrose Hepática Biliar/diagnóstico , Transplante de Fígado , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/mortalidade , Doenças Autoimunes/terapia , Bezafibrato/uso terapêutico , Biomarcadores/sangue , Biomarcadores/metabolismo , Biópsia , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/uso terapêutico , Progressão da Doença , Quimioterapia Combinada/métodos , Técnicas de Imagem por Elasticidade , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/mortalidade , Fadiga/diagnóstico , Fadiga/imunologia , Fadiga/terapia , Feminino , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Fígado/diagnóstico por imagem , Fígado/enzimologia , Fígado/imunologia , Fígado/patologia , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/mortalidade , Cirrose Hepática Biliar/terapia , Testes de Função Hepática , Pessoa de Meia-Idade , Uso Off-Label , Prognóstico , Prurido/diagnóstico , Prurido/imunologia , Prurido/terapia , Qualidade de Vida , Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/terapia , Taxa de Sobrevida , Resultado do Tratamento , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
Morinda citrifolia, a fruit generally known as "Noni", has been traditionally used in parts of East Asia to relieve inflammatory diseases. Although several studies using noni have been reported, the effect of fermented Morinda citrifolia (F.NONI) on atopic dermatitis (AD) has not been investigated. Thus, we aimed to investigate the improving effect of F.NONI treatment on AD-like skin lesions and elucidate molecular mechanisms. F.NONI was prepared by the fermentation of noni fruit with probiotics and then extracted. F.NONI was orally administrated to NC/Nga mice to evaluate its therapeutic effect on 2,4-dinitrochlorobenzene (DNCB)-induced AD. Oral administration of F.NONI significantly alleviated AD lesions and symptoms such as dermatitis scores, ear thickness, scratching behavior, epidermal thickness, and infiltration of inflammatory cells (e.g., mast cells and eosinophils). In addition, F.NONI treatment reduced the levels of histamine, IgE and IgG1/IgG2a ratio, thymus and activation regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP) in serum and beneficially modulated the expressions of Th1, Th2, Th17, and Th22-mediated cytokines in lesioned skin and splenocytes. Furthermore, the expressions of the skin barrier-related proteins including filaggrin (FLG), loricrin (LOR), involucrin (IVL), zonula occludens-1 (ZO-1), and occludin (OCC) were restored by F.NONI treatment. Taken together, these results suggest that F.NONI could be a therapeutic agent to attenuate AD-like skin lesions through modulating the immune balance and skin barrier function.
Assuntos
Anti-Inflamatórios/farmacologia , Dermatite Atópica/prevenção & controle , Fermentação , Morinda , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Citocinas/sangue , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dinitroclorobenzeno , Modelos Animais de Doenças , Proteínas Filagrinas , Frutas , Histamina/sangue , Imunoglobulina G/sangue , Proteínas de Filamentos Intermediários/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Ocludina/metabolismo , Extratos Vegetais/isolamento & purificação , Precursores de Proteínas/metabolismo , Prurido/induzido quimicamente , Prurido/imunologia , Prurido/metabolismo , Prurido/prevenção & controle , Pele/imunologia , Pele/metabolismo , Pele/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Proteína da Zônula de Oclusão-1/metabolismoAssuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Conjuntivite/epidemiologia , Dermatite Atópica/tratamento farmacológico , Prurido/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Conjuntivite/induzido quimicamente , Conjuntivite/imunologia , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prurido/diagnóstico , Prurido/imunologia , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disorder characterized by destruction of liver bile ducts leading to intrahepatic cholestasis. It causes intractable pruritus for which ultraviolet (UV)B phototherapy is an experimental treatment when alternative therapies fail. The pathophysiology of cholestatic itch and the mechanism of action of narrowband UVB in this condition remains poorly understood. OBJECTIVES: To summarize the current literature and propose testable hypotheses for the mechanism of action of phototherapy in attenuating itch. METHODS: A focused PubMed search for articles relating to the pathogenesis of itch in cholestatic disease was performed. A total of 3855 articles were screened and 50 were found suitable for literature review. Evidence from this literature review was combined with author expertise in the area. RESULTS: Formulated hypotheses focus on the role of bile salts, autotaxin and specific receptors including G-protein-coupled bile acid receptor, Gpbar1 (also known as TGR5) and the nuclear transcription factor farnesoid X receptor. CONCLUSIONS: Several testable mechanisms through which phototherapy may exert its effects are discussed in this review. The next steps are to carry out an objective assessment of the efficacy of phototherapy in cholestatic pruritus, gain further knowledge on the underlying pathways, and subsequently trial its use against current licensed therapies. Such studies could lead to increased mechanistic understanding, identification of novel therapeutic targets and the potential to refine phototherapy protocols, leading to improved control of itch and quality of life in patients with PBC. What's already known about this topic? Primary biliary cholangitis (PBC) is frequently associated with intractable pruritus for which current treatment options are often unsuccessful. Phototherapy is used as an experimental treatment for PBC-associated pruritus when alternative better-studied treatments fail. What does this study add? This study reviews the current literature on the pathophysiology and management of cholestatic pruritus, an area which remains poorly understood. We propose testable hypotheses of the mechanisms behind the attenuation of cholestatic pruritus with phototherapy.
Assuntos
Cirrose Hepática Biliar/complicações , Prurido/imunologia , Pele/imunologia , Terapias em Estudo/métodos , Terapia Ultravioleta/métodos , Ácidos e Sais Biliares/imunologia , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/efeitos da radiação , Humanos , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/imunologia , Lisofosfolipídeos/imunologia , Lisofosfolipídeos/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Prurido/sangue , Prurido/patologia , Prurido/radioterapia , Receptor PAR-2/metabolismo , Eliminação Renal/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos , Pele/patologia , Pele/efeitos da radiação , Resultado do Tratamento , Triptases/metabolismoRESUMO
Background Conduct a pilot study addressing the efficacy of acupuncture in the treatment of chronic idiopathic pruritus to aid in the design of a larger clinical trial. Routine laboratory tests to assess systemic inflammation in addition to subjective patient surveys were performed provide documentation of efficacy of treatment. Methods Patients with chronic pruritus who did not respond to standard treatment were recruited to participate. After exclusion of systemic or known reversible causes, each patient received up to 10 treatments which were performed approximately one week apart. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured before and after a series of acupuncture treatments to evaluate levels of inflammation and pre- and post-treatment surveys were conducted to evaluate levels of perceived itch. Results Only one of the ten patients in this study possessed an elevation of ESR before treatment. This patient's ESR value returned to normal range after treatment and this participant reported subjective relief of her pruritus. Conclusions Future studies on the efficacy of acupuncture in the treatment of chronic idiopathic pruritus should focus on those patients with measurable levels of inflammation at the initiation of the study or utilize alternative and more comprehensive values to monitor disease response.
Assuntos
Terapia por Acupuntura , Prurido/terapia , Adulto , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , Doença Crônica/terapia , Feminino , Humanos , Masculino , Projetos Piloto , Prurido/sangue , Prurido/imunologia , Resultado do Tratamento , Adulto JovemRESUMO
Atopic dermatitis (AD) is the most common itchy dermatosis that affects millions of children and adults worldwide. Chronic itch in this condition has significant impact on measures of quality of life, such as sleep. Treating itch in AD has been challenging for decades, but new drugs have emerged in the last year with significant anti-pruritic effect. The optimal treatment regimen for atopic itch addresses barrier dysfunction, inflammation, neural hypersensitivity, and the itch-scratch cycle. Topical moisturizers remain the foundation of treatment and should be used by all patients with AD-associated pruritus. Step-wise therapy, from topical anti-inflammatory creams to systemic monoclonal antibodies and immunosuppressants, is recommended. There are multiple adjuvant therapies that can be used, especially to target itch in the setting of minimal skin inflammation. Finally, patient education, sleep management, and stress relief are important components to optimize outcomes. This review assesses the latest advances and treatment recommendations for pruritus in AD. Finally, suggested therapeutic ladders and emerging treatments are discussed.
Assuntos
Dermatite Atópica/terapia , Fármacos Dermatológicos/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Sistema Nervoso/efeitos dos fármacos , Prurido/terapia , Administração Cutânea , Administração Oral , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Bandagens , Dermatite Atópica/complicações , Dermatite Atópica/patologia , Fármacos Dermatológicos/farmacologia , Proteínas Filagrinas , Humanos , Hipersensibilidade/imunologia , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismo , Sistema Nervoso/imunologia , Educação de Pacientes como Assunto , Fototerapia/métodos , Prurido/etiologia , Prurido/imunologia , Prurido/patologia , Qualidade de Vida , Pele/efeitos dos fármacos , Pele/imunologia , Pele/inervação , Pele/patologia , Creme para a Pele/uso terapêuticoRESUMO
Pruritus is the major symptom of ocular allergy but currently available treatments are often ineffective. Previous studies demonstrated that subpopulations of primary sensory neurons express Fc receptors and may contribute to antigen-specific pain. We investigated the role of neuronal Fc-epsilon Receptor I (FcεRI) in allergic ocular pruritus. Ovalbumin (OVA) was used as allergen together with alum adjuvant (OVA+alum) to produce a mouse model of ocular allergy with a significant elevation in the serum levels of both antigen-specific IgE and IgG. Mice sensitized by OVA without alum only induced elevation of serum IgG but not IgE. Scratching behavior toward the eyes with the hindlimb was used as an indicator of ocular itch. Topical OVA challenging to the eye dose-dependently induced scratching toward the eye in the OVA+alum sensitized mice, but not those sensitized by OVA only. The antigen-induced scratching was largely abolished by topical application of the blocking antibody to FcεRIα, but was only partially alleviated by pretreatment of mast cell stabilizer or histamine I receptor antagonist. The expression of FcεRI was detected in subpopulations of trigeminal ganglion (TG) neurons including those expressing pruriceptive markers and innervating the conjunctiva in the naïve mice. Moreover, FcεRI was found significantly upregulated in small-sized TG neurons in the OVA+alum sensitized mice. In acutely dissociated TG neurons, IgE-immune complex (IC), but not the antibody or antigen alone, induced intracellular calcium increase. The neuronal responses to IgE-IC could be specifically blocked by pre-application of a siRNA for FcεRIα. Our results indicate that FcεRI expressed on peripheral nociceptive neurons in the TG may be directly activated by IgE-IC and contribute to allergic ocular pruritus. This study may suggest a novel mechanism for the development of pathological itch in allergic diseases.
Assuntos
Oftalmopatias/metabolismo , Hipersensibilidade/metabolismo , Neurônios/metabolismo , Prurido/metabolismo , Receptores de IgE/metabolismo , Compostos de Alúmen , Animais , Modelos Animais de Doenças , Oftalmopatias/imunologia , Hipersensibilidade/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/imunologia , Ovalbumina , Prurido/imunologiaRESUMO
BACKGROUND: Clinical evidence suggests that acupuncture improves symptoms in persistent allergic rhinitis, but the physiologic basis of these improvements is not well understood. OBJECTIVE: A randomized, sham-controlled trial of acupuncture for persistent allergic rhinitis in adults investigated possible modulation of mucosal immune responses. METHODS: A total of 151 individuals were randomized into real and sham acupuncture groups (who received twice-weekly treatments for 8 weeks) and a no acupuncture group. Various cytokines, neurotrophins, proinflammatory neuropeptides, and immunoglobulins were measured in saliva or plasma from baseline to 4-week follow-up. RESULTS: Statistically significant reduction in allergen specific IgE for house dust mite was seen only in the real acupuncture group, from 18.87 kU/L (95% CI, 10.16-27.58 kU/L) to 17.82 kU/L (95% CI, 9.81-25.83 kU/L) (P = .04). A mean (SE) statistically significant down-regulation was also seen in proinflammatory neuropeptide substance P (SP) 18 to 24 hours after the first treatment from 408.74 (299.12) pg/mL to 90.77 (22.54) pg/mL (P = .04). No significant changes were seen in the other neuropeptides, neurotrophins, or cytokines tested. Nasal obstruction, nasal itch, sneezing, runny nose, eye itch, and unrefreshed sleep improved significantly in the real acupuncture group (postnasal drip and sinus pain did not) and continued to improve up to 4-week follow-up. CONCLUSION: Acupuncture modulated mucosal immune response in the upper airway in adults with persistent allergic rhinitis. This modulation appears to be associated with down-regulation of allergen specific IgE for house dust mite, which this study is the first to report. Improvements in nasal itch, eye itch, and sneezing after acupuncture are suggestive of down-regulation of transient receptor potential vanilloid 1. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier: ACTRN 12610001052022.
Assuntos
Terapia por Acupuntura , Rinite Alérgica/terapia , Adolescente , Adulto , Alérgenos/imunologia , Animais , Citocinas/sangue , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Neuropeptídeos/imunologia , Poaceae/imunologia , Pólen/imunologia , Prurido/sangue , Prurido/imunologia , Prurido/terapia , Pyroglyphidae/imunologia , Qualidade de Vida , Mucosa Respiratória/imunologia , Rinite Alérgica/sangue , Rinite Alérgica/imunologia , Saliva/química , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
Angelica sinensis (AS) is one of the most popular medicinal foods used as a hematopoietic herb and also traditionally applied topically for skin disorders. However, the effectiveness of AS on atopic dermatitis (AD) has not been reported yet. This study was conducted to evaluate the antipruritic and anti-inflammatory effects of AS on regulating AD-related mediators in DNCB (2,4-dinitrochlorobenzene)-induced mice. AS was topically applied to the dorsal skin of DNCB-challenged mice for 11 days. Alteration of skin thickness was measured for assessment of histological improvement. In addition, the number of mast cells, the level of serum immunoglobulin E (IgE), the counting of scratching behavior, and the expression of substance P were evaluated. Also, the expressions of cytokines, nuclear factor κB (NF-κB), phospho-IκBα, and mitogen-activated protein kinases (MAPKs) were measured for evaluating the improvement of skin inflammation. The repeated treatment of AS significantly inhibited the skin thickness, the number of mast cells, and the level of serum IgE. Moreover, AS significantly suppressed the increased scratching behavior and the expression of substance P compared to the DNCB group. Topical application of AS also reduced the level of cytokines (IL-4, IL-6, TNF-α, and IFN-γ) as well as the expressions of NF-κB, phospho-IκBα, and phospho-MAPKs in the dorsal skin. The results of our study suggest that topical application of AS might have efficacy for modulating pruritus and inflammation in AD. Further studies are required to further characterize the mechanism of actions of AS.
Assuntos
Angelica sinensis/química , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/imunologia , Extratos Vegetais/administração & dosagem , Prurido/tratamento farmacológico , Prurido/imunologia , Animais , Dermatite Atópica/genética , Feminino , Humanos , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , NF-kappa B/imunologia , Prurido/genética , Pele/efeitos dos fármacos , Pele/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: It has frequently been speculated that pruritus and skin lesions develop after topical exposure to aeroallergens in sensitized patients with atopic dermatitis (AD). OBJECTIVE: We sought to study cutaneous reactions to grass pollen in adult patients with AD with accompanying clear IgE sensitization to grass allergen in an environmental challenge chamber using a monocenter, double-blind, placebo-controlled study design. METHODS: Subjects were challenged on 2 consecutive days with either 4000 pollen grains/m(3) of Dactylis glomerata pollen or clean air. The severity of AD was assessed at each study visit up to 5 days after challenge by (objective) scoring of AD (SCORAD). Additionally, air-exposed and non-air-exposed skin areas were each scored using local SCORAD scoring and investigator global assessments. Levels of a series of serum cytokines and chemokines were determined by using a Luminex-based immunoassay. The primary end point of the study was the change in objective SCORAD scores between prechallenge and postchallenge values. RESULTS: Exposure to grass pollen induced a significant worsening of AD. A pronounced eczema flare-up of air-exposed rather than covered skin areas occurred. In grass pollen-exposed subjects a significantly higher increase in CCL17, CCL22, and IL-4 serum levels was observed. CONCLUSIONS: This study demonstrates that controlled exposure to airborne allergens of patients with a so-called extrinsic IgE-mediated form of AD induced a worsening of cutaneous symptoms.
Assuntos
Dermatite Atópica/imunologia , Eczema/imunologia , Prurido/imunologia , Adulto , Alérgenos/efeitos adversos , Alérgenos/imunologia , Câmaras de Exposição Atmosférica/efeitos adversos , Quimiocina CCL17/sangue , Quimiocina CCL22/sangue , Dactylis , Progressão da Doença , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Imunoglobulina E/sangue , Interleucina-4/sangue , Masculino , Pólen/imunologia , Adulto JovemRESUMO
Full spectrum light (FSL) includes UVA, visible light and infrared light. Many studies have investigated the application of FSL in severe cases of atopic dermatitis (AD) in humans; however, FSL has not yet been studied in an animal model. The purpose of this study was to evaluate the therapeutic effects of FSL on AD-like skin lesions using NC/Nga mice, with the aim of mitigating itching and attenuating the expression of adhesion molecules. We examined the effects of FSL on mite allergen-treated NC/Nga mice by assessing skin symptom severity, ear thickness, serum IgE levels, and the cytokine expression. We examined the histology of lesions using hematoxylin-eosin, toluidine blue and immunohistochemical staining. Our findings suggest that FSL phototherapy exerts positive therapeutic effects on Dermatophagoides farinae (Df)-induced AD-like skin lesions in NC/Nga mice by reducing IgE levels, thus promoting recovery of the skin barrier. The mechanisms by which FSL phototherapy exerts its effects may also involve the inhibition of scratching behavior, reduction of IL-6 levels and reductions in adhesion molecule expression. The present study indicates that FSL phototherapy inhibits the development of AD in NC/Nga mice by suppressing cytokine, chemokine and adhesion molecule expression, and thus, could potentially be useful in treating AD.
Assuntos
Dermatite Atópica/radioterapia , Fototerapia/métodos , Prurido/radioterapia , Pele/efeitos da radiação , Alérgenos/imunologia , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Dermatophagoides farinae/imunologia , Modelos Animais de Doenças , Orelha/patologia , Orelha/efeitos da radiação , Expressão Gênica , Histocitoquímica , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/imunologia , Interleucina-1beta/sangue , Interleucina-1beta/imunologia , Interleucina-4/sangue , Interleucina-4/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Luz , Masculino , Camundongos , Prurido/induzido quimicamente , Prurido/imunologia , Prurido/patologia , Pele/imunologia , Pele/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologiaAssuntos
Hipersensibilidade Alimentar/imunologia , Hipersensibilidade ao Látex/imunologia , Lycium/imunologia , Fosfopiruvato Hidratase/imunologia , Prurido/imunologia , beta-Glucosidase/imunologia , Adulto , Alérgenos/efeitos adversos , Alérgenos/imunologia , Proteínas de Transporte/efeitos adversos , Proteínas de Transporte/imunologia , Feminino , Hipersensibilidade Alimentar/diagnóstico , Frutas/efeitos adversos , Humanos , Imunoglobulina E/sangue , Látex/efeitos adversos , Hipersensibilidade ao Látex/diagnóstico , Fosfopiruvato Hidratase/efeitos adversos , Fosfopiruvato Hidratase/isolamento & purificação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Prurido/diagnóstico , Prurido/etiologia , Testes Cutâneos , Síndrome , beta-Glucosidase/efeitos adversos , beta-Glucosidase/isolamento & purificaçãoRESUMO
An insect-bite-like reaction is known to occur in patients with chronic lymphocytic leukemia (CLL). Most of the literature, however, consists of isolated case reports or small case series. The aim of this retrospective study was to review the national experience with insect-bite-like reaction in a large group of patients with CLL. The study cohort of patients with these skin reactions consisted of 48 patients (25 males, 23 females) of mean age 64.8 yr (range 33-89) at skin eruption. Data on clinical, histologic, immunophenotypic, and cytogenetic characteristics, treatment, and outcome were collected from the medical files. Mean time between diagnosis of CLL and appearance of the skin lesions was 3.1 yr (range -4 to 14 yr). The eruption was not related to disease activity or the course of the hematological disease. The eruption preceded the diagnosis of CLL in 10 patients (by 0-4 yr); and followed the diagnosis in 36; in 11 patients, it occurred during therapy for CLL and in nine after therapy. Mean duration of the skin findings was 21.5 months (range 0.3-132). The eruption usually presented in summer, although it occurred also at other times of the year, and predominantly affected the upper and lower limbs, although it also appeared on unexposed areas. Treatment included local ointments, antihistaminics, oral steroids, antibiotics, phototherapy, and dapsone with varying responses. Insect-bite-like reactions is a relatively common and disturbing skin reaction in CLL patients, it may be related to the immune dysregulation accompanying CLL and further exacerbated by external factors, including actual insect bites, chemoimmunotherapy, and pyogenic infection.
Assuntos
Mordeduras e Picadas de Insetos/diagnóstico , Leucemia Linfocítica Crônica de Células B/diagnóstico , Dermatopatias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Exantema/diagnóstico , Exantema/tratamento farmacológico , Exantema/imunologia , Exantema/patologia , Feminino , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Prurido/diagnóstico , Prurido/tratamento farmacológico , Prurido/imunologia , Prurido/patologia , Estudos Retrospectivos , Dermatopatias/tratamento farmacológico , Dermatopatias/imunologia , Dermatopatias/patologia , Esteroides/uso terapêuticoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The root of Panax ginseng CA Meyer (ginseng) has been used for diabetes, cancer, stress and allergic diseases in the traditional Chinese medicine. AIM OF THE STUDY: To understand the role of intestinal microflora in the pharmacological effect of ginsenoside Re, which is a main constituent of ginseng, we investigated its anti-scratching behavioral effect in the mice treated with or without antibiotics. MATERIALS AND METHODS: Ginsenoside Re was orally administered to the mice treated with antibiotics (cefadroxil, oxytetracycline and erythromycin mixture (COE), streptomycin or/and tetracycline) and then investigated the relationship between ginsenoside Re-metabolizing ß-glucosidase and α-rhamnosidase activities of intestinal microflora and its antiscratching behavioral effect. The anti-scratching behavioral effects of ginsenosides were investigated in the increments of 1 h and 6 h after their oral administrations. The scratching behavioral frequency was measured for 1 h after treatment with histamine. RESULTS: Ginsenoside Re inhibited histamine-induced scratching behavior in mice. The anti-scratching behavioral effect of ginsenoside Re was more potent 6 h after its oral administration than 1 h after. However, its inhibitory effect was significantly attenuated in mice treated with COE, but it nearly was not affected in mice treated with streptomycin and/or tetracycline. Treatment with COE also significantly lowered fecal ginsenoside Re-metabolizing ß-glucosidase and α-rhamnosidase activities in mice, as well as fecal metabolic activity of ginsenoside Re to ginsenoside Rh1. The anti-scratching behavioral effect of ginsenoside Rh1, a metabolite of ginsenoside Re by intestinal microflora, was superior to that of ginsenoside Re. Ginsenoside Rh1 potently inhibited the expression of IL-4 and TNF-α, as well as the activation of NF-κB and c-jun activation in histamine-stimulated scratching behavioral mice. CONCLUSION: Ginsenoside Re may be metabolized to ginsenoside Rh1 by intestinal microflora, which enhances its anti-scratching behavioral effect by inhibiting NF-κB and c-jun activations.
Assuntos
Antibacterianos/farmacologia , Comportamento Animal/efeitos dos fármacos , Ginsenosídeos/farmacologia , Adulto , Idoso , Animais , Antialérgicos/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Fezes/enzimologia , Fezes/microbiologia , Feminino , Ginsenosídeos/isolamento & purificação , Glicosídeo Hidrolases/metabolismo , Histamina/farmacologia , Humanos , Interleucina-4/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pessoa de Meia-Idade , Ftalazinas/farmacologia , Prurido/induzido quimicamente , Prurido/imunologia , Prurido/fisiopatologia , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem , beta-Glucosidase/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Chamomile is most popular used medicinal plant and extensively consumed as a tea or tisanes. Traditionally this plant was used for treatment of many ailments such as allergy disorders and inflammatory mediated diseases. AIM OF THE STUDY: We investigated the effects of anti-allergic activity of Matricaria recutita L. on mast cell mediated allergic models. MATERIALS AND METHODS: The protective effect of methanol extract of Matricaria recutita against compound 48/80 induced anaphylaxis and pruritis models for acute phase of hypersensitivity reactions were carried out. The late phase hypersensitivity reactions by compound 48/80 induced mast cell degranulation and histamine release from blood along with serum nitric oxide (NO), rat peritoneal fluid nitric oxide (NO) and bronchoalveolar fluid nitric oxide (NO) levels were measured. RESULTS: The methanol extract of Matricaria recutita L. showed inhibitory effects on anaphylaxis induced by compound 48/80 and significant dose dependent anti-pruritis property was observed by inhibiting the mast cell degranulation. Mast cell membrane stabilization activity was also observed in compound 48/80 induced mast cell activation. Dose dependent reduction in the histamine release, along with decreased release of serum, rat peritoneal and BAL fluid nitric oxide (NO) levels were observed. CONCLUSION: These results suggest that the methanol extract of Matricaria recutita showed potent anti-allergic activity by inhibition of histamine release from mast cells.
Assuntos
Anafilaxia/prevenção & controle , Antialérgicos/farmacologia , Hipersensibilidade/prevenção & controle , Mastócitos/efeitos dos fármacos , Matricaria , Extratos Vegetais/farmacologia , Prurido/prevenção & controle , Anafilaxia/sangue , Anafilaxia/imunologia , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Líquido Ascítico/metabolismo , Líquido da Lavagem Broncoalveolar/química , Degranulação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/sangue , Hipersensibilidade/imunologia , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Matricaria/química , Metanol/química , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/sangue , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Prurido/sangue , Prurido/imunologia , Ratos , Ratos Sprague-Dawley , Solventes/química , p-Metoxi-N-metilfenetilaminaRESUMO
Atopic dermatitis (AD) is a common inflammatory skin disorder for which few safe and effective systemic treatments are available. To test the clinical and immunomodulatory effects of a crude polysaccharide fraction isolated from Dendrobium huoshanense for the treatment of AD, we conducted a pilot, uncontrolled case series study. Twenty-seven patients aged 4-18 years (mean∓SD, 10.82±4.4) with AD that had not responded to topical therapy were treated with polysaccharide derived from D. huoshanense for 4 weeks and followed-up for another 4 weeks. Progression of AD was determined with the Lund-Browder chart for children, the Investigator's Global Atopic Dermatitis Assessment (IGADA), and the Scoring Atopic Dermatitis (SCORAD) at weeks 0, 2, 4, and 8. Serum levels of cytokines were evaluated. Safety was determined with laboratory and clinical tests. The lesion area, IGADA score, total SCORAD result, and score for sleeplessness decreased significantly from weeks 0 to 4, but did not change significantly between weeks 4 and 8. The scores for subjective symptoms and pruritus decreased significantly from week 0 to week 4 and increased significantly from week 4 to week 8. Serum levels of IL-5, IL-13, IFN-gamma, and TGF-beta1 decreased significantly between weeks 0 and 4 and between weeks 0 and 8. No significant difference in the levels of IL-10 was found. The polysaccharide from D. huoshanense reduced the levels of some cytokines associated with AD and had beneficial effects on symptoms. No serious adverse effects occurred when it was administered orally for 4 weeks.
Assuntos
Dendrobium , Dermatite Atópica/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Administração Oral , Adolescente , Criança , Pré-Escolar , Citocinas/sangue , Dendrobium/química , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/isolamento & purificação , Masculino , Projetos Piloto , Extratos Vegetais/efeitos adversos , Polissacarídeos/efeitos adversos , Polissacarídeos/isolamento & purificação , Prurido/imunologia , Prurido/prevenção & controle , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/imunologia , Distúrbios do Início e da Manutenção do Sono/prevenção & controle , Taiwan , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE AND METHODS: The crucial symptom of atopic eczema is itch. Acupuncture has been shown to exhibit a significant effect on experimental itch; however, studies focusing on clinical itch in atopic eczema and corresponding mechanisms are lacking. The study design was a unicenter, single-blinded (observer), prospective, randomized clinical pilot trial with an additional experimental part. In 10 patients with atopic eczema, we investigated the effect of acupuncture treatment (n = 5) compared to no treatment (n = 5) on itch intensity and in vitro basophil CD63 expression upon allergen stimulation (house dust mite and timothy grass pollen) in a pilot trial. RESULTS: Mean itch intensity in a visual analog scale was rated significantly lower in the acupuncture group (-25% ± 26% [day 15-day 0]; -24% ± 31% [day 33-day 0]) than in the control group (15% ± 6% [day 15-day 0]; 29% ± 9% [day 33-day 0]). From day 0 (before treatment) to day 15 (after 5 acupuncture treatments) as well as day 33 (after 10 acupuncture treatments), the acupuncture group showed less CD63 positive basophils than the control group regarding stimulation with house dust mite and grass pollen allergen at various concentrations (5 ng/mL, 1 ng/mL, 0.5 ng/mL, or 0.25 ng/mL). CONCLUSIONS: Our results show a reduction of itch intensity and of in vitro allergen-induced basophil activation in patients with atopic eczema after acupuncture treatment. Reducing basophil activation can be a further tool in investigating the mechanisms of action of acupuncture in immunoglobulin E-mediated allergy. Due to the limited number of patients included in our pilot trial, further studies are needed to strengthen the hypothesis.