RESUMO
BACKGROUND: α-melanocyte-stimulating hormone (α-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils. OBJECTIVE: This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of α-MSH in human basophils especially from patients with allergic rhinitis. METHODS: MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay. RESULTS: We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response.
Assuntos
Receptor Tipo 1 de Melanocortina/metabolismo , Rinite Alérgica/imunologia , Rinite Alérgica/metabolismo , Adulto , Alérgenos/imunologia , Animais , Basófilos/imunologia , Basófilos/metabolismo , Biópsia , Quimiotaxia/imunologia , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Imunoglobulina E/imunologia , Masculino , Camundongos , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Testes de Provocação Nasal , Diester Fosfórico Hidrolases/metabolismo , Pólen/imunologia , Pirofosfatases/metabolismo , Receptor Tipo 1 de Melanocortina/genética , Testes de Função Respiratória , Rinite Alérgica/diagnóstico , Rinite Alérgica/genética , Testes Cutâneos , Adulto Jovem , alfa-MSH/metabolismoRESUMO
BACKGROUND: Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment. METHODS: Patients (7.9-64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG(4) measured. RESULTS: Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8-92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between -11.3% and -14.8% for placebo (P < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and -1.51% for placebo (P < 0.05). Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT continued during follow up. Increases in specific IgG(4) observed in the first season were sustained for SLIT vs placebo throughout treatment (P = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported. CONCLUSIONS: Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT.
Assuntos
Alérgenos/administração & dosagem , Dessensibilização Imunológica/métodos , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Administração Sublingual , Adolescente , Adulto , Idoso , Alérgenos/efeitos adversos , Criança , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Estações do Ano , Adulto JovemRESUMO
BACKGROUND: Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment. METHODS: Patients (7.9-64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG(4) measured. RESULTS: Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8-92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between -11.3% and -14.8% for placebo (P < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and -1.51% for placebo (P < 0.05). Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT continued during follow up. Increases in specific IgG(4) observed in the first season were sustained for SLIT vs placebo throughout treatment (P = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported. CONCLUSIONS: Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT.
Assuntos
Imunoterapia/métodos , Poaceae , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Administração Sublingual , Adolescente , Adulto , Criança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Imunoterapia/efeitos adversos , Pessoa de Meia-Idade , Estações do Ano , Fatores de Tempo , Titulometria , Resultado do Tratamento , Adulto JovemRESUMO
Hand eczema (HE) is one of the most frequent skin diseases. HE has a wide spectrum, with variable etiology, severity, and morphology. It often displays a chronically relapsing course with a poor prognosis, and has a high impact on the quality of life. Although different treatment options exist, the management of patients with chronic HE is often unsatisfactory. We highlight new and rarely used approaches to treat chronic HE uncluding local UVA-1-phototherapy, retinoids including the new oral retinoid alitretinoin, and calcineurin inhibitors.
Assuntos
Inibidores de Calcineurina , Fármacos Dermatológicos/uso terapêutico , Eczema/terapia , Dermatoses da Mão/terapia , Retinoides/uso terapêutico , Terapia Ultravioleta/tendências , Administração Oral , Doença Crônica , Humanos , RecidivaRESUMO
BACKGROUND: Patients with allergic rhinitis (AR) feature both allergic airway inflammation and a hyperresponsiveness to nonspecific stimuli which is partly neuronally controlled. Still, it is unclear whether or not neurotrophins are involved in airway pathophysiology of AR and in nasobronchial interaction. METHODS: Nine AR patients with mono-allergy to grass pollen and nine healthy controls underwent nasal allergen provocation (NP). Serum samples, nasal and bronchial biopsies were taken before (T(0)) and 24 h after (T(24)) NP. Pan-neurotrophin receptor p75(NTR), tyrosine kinase A (trkA), trkB, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were assessed with immunohistochemistry, and NGF and BDNF levels with ELISA. RESULTS: At T(24), BDNF and NGF were upregulated in nasal mucosa (P < 0.05) and increased in the peripheral blood of AR compared with T(0). The increase in nasal BDNF expression correlated positively with the maximum increase in total nasal symptom score in AR (P = 0.02). p75(NTR) was expressed on peripheral nerves and epithelial layer, trkA on endothelial cells, and trkB on mast cells. trkB + mast cells significantly decreased after NP in AR (P < 0.01). NP did not modulate p75(NTR) and trkA expression in nasal mucosa and had no effect on the expression of neurotrophins and receptors in bronchial mucosa. CONCLUSION: This study shows that neurotrophins and their receptors are expressed in human airways. Allergic rhinitis was characterized by a modulation of BDNF, NGF, and trkB in nasal mucosa after NP and a correlation of nasal BDNF with the maximal increase of total nasal symptom score. Therefore, our data suggest that neurotrophins participate in upper-airway pathophysiology in AR, whereas their role in nasobronchial interaction remains unclear.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/imunologia , Fator de Crescimento Neural/imunologia , Receptor de Fator de Crescimento Neural/imunologia , Receptor trkA/imunologia , Receptor trkB/imunologia , Mucosa Respiratória/imunologia , Rinite Alérgica Sazonal/imunologia , Adulto , Alérgenos , Fator Neurotrófico Derivado do Encéfalo/sangue , Brônquios/imunologia , Feminino , Humanos , Masculino , Mastócitos/imunologia , Cavidade Nasal/imunologia , Testes de Provocação Nasal , Fator de Crescimento Neural/sangue , Poaceae/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/sangueRESUMO
There are very few reports on allergic reactions to lychee fruit in the literature. We describe the case of a 26-year-old man who developed pruritus, generalized urticaria, and severe angioedema of his lips and tongue with dyspnea within 15 minutes after lychee fruit intake. Although we found no lychee-specific immunoglobulin E antibodies, a basophil activation test (BAT) and a cellular antigen stimulation test (CAST) to lychee were both positive, as was a prick-to-prick test with fresh lychee fruit. The patient also suffered from an oral food allergy syndrome to parsley and was sensitized to mugwort but not to latex or profilin. BAT and CAST are helpful tools in the diagnostic workup for exotic food allergy. Mugwort is suggested as the allergen responsible for,the cross-reactivity presented by this patient, as he had no sensitization to latex or profilin.
Assuntos
Anafilaxia/etiologia , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/diagnóstico , Litchi/efeitos adversos , Adulto , Antígenos CD/metabolismo , Artemisia/efeitos adversos , Basófilos/imunologia , Basófilos/metabolismo , Reações Cruzadas , Citometria de Fluxo , Hipersensibilidade Alimentar/imunologia , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina E/sangue , Leucotrienos/biossíntese , Masculino , Petroselinum/efeitos adversos , Glicoproteínas da Membrana de Plaquetas/metabolismo , Testes Cutâneos , Tetraspanina 30RESUMO
Atopic dermatitis is a chronic inflammatory skin disease which often persists until adulthood. In severe cases, eczematous lesions and pruritus are resistant to therapy and result in depression, impairment of professional activities and social withdrawal. The goal of inpatient rehabilitation measures is to keep the patient involved and active in professional and social activities. Rehabilitative measures include diagnostics and medical therapy according to current guidelines, instruction in basic medical information, psychological intervention (relaxation techniques, improvement of self-confidence), dietetic measures, exercise, and social advice. Patients with atopic dermatitis often have work-related problems which should be identified as early as possible during rehabilitation.
Assuntos
Dermatite Atópica/reabilitação , Dermatite Atópica/diagnóstico , Dermatite Atópica/psicologia , Dieta , Exercício Físico , Humanos , Pacientes Internados , Educação de Pacientes como Assunto , Garantia da Qualidade dos Cuidados de Saúde , Terapia de Relaxamento , Fatores de TempoRESUMO
This guideline is the result of a consensus reached during a panel discussion at the second International Consensus Meeting on Urticara, Urticaria 2004, a joint initiative of the EAACI Dermatology Section and GA2LEN. Urticaria has a profound impact on the quality of life, and effective treatment is therefore required. The recommended first line treatment are nonsedating H1 antihistamines. They have proven to be effective in double-blind controlled studies, but dosages increased up to fourfold over the recommended doses may be necessary. However, for different urticaria subtypes and in view of individual variation in the course of the disease and response to treatment, additional or alternative therapies may be required. Immunosuppressive drugs like cyclosporin A and corticosteroids are not recommended for long-term treatment due to unavoidable severe adverse effects. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and formally approved by the European Union of Medical Specialists (UEMS).
Assuntos
Antialérgicos/uso terapêutico , Dieta , Imunossupressores/uso terapêutico , Qualidade de Vida , Urticária/terapia , Terapia Combinada , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Estilo de Vida , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Urticária/diagnósticoRESUMO
BACKGROUND: Food allergy to cow's milk or hen's egg is a common problem in children with atopic eczema/dermatitis syndrome (AEDS) but the role of birch pollen-related food for the induction of allergic symptoms is still not clear. PATIENTS/METHODS: Twelve children (median age 5 years) with AEDS underwent an oral challenge with those birch pollen-related foods which were reported to induce no immediate symptoms, but were consumed on a regular basis. Total IgE and specific IgE to birch pollen, Bet v 1/2 and various birch pollen-related foods were determined. RESULTS: Seven of 12 children showed immediate and/or late eczematous reactions upon ingestion of birch pollen-related foodstuff. Four children showed a worsening of eczema 24 h upon oral challenge with a significant difference in SCORAD before and after challenge. There were no differences in terms of total IgE or birch pollen-specific IgE between children with a late eczematous response and non-reacting children. CONCLUSIONS: Birch pollen-related food may induce allergic symptoms in children with AEDS who exhibit a sensitization to birch pollen. Oral challenge tests should be performed in those children who suffer from severe AEDS and who are highly sensitized to birch pollen allergens even in the absence of a history suggestive of food allergy.
Assuntos
Betula/imunologia , Dermatite Atópica/etiologia , Hipersensibilidade Alimentar/complicações , Pólen/imunologia , Alérgenos/imunologia , Antígenos de Plantas , Criança , Pré-Escolar , Humanos , Imunoglobulina E/sangue , Proteínas de Plantas/imunologiaRESUMO
The optimal treatment of atopic dermatitis requires regular medical supervision. The course of this chronic skin disease is influenced by multiple triggers which are relevant for the treatment. The mainstays of topical therapy include regular use of emollients coupled with antimicrobial substances, corticosteroids and immune modulators as required. Ultraviolet radiation and immunosuppressive regimens represent further options for the treatment of severe exacerbations and may lead to long term improvement. Data from experimental studies provide insight into possible future treatment methods.
Assuntos
Dermatite Atópica/terapia , Ácido Micofenólico/análogos & derivados , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Adolescente , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Fatores Etários , Animais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Azatioprina/administração & dosagem , Azatioprina/uso terapêutico , Criança , Pré-Escolar , Estudos Cross-Over , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Dessensibilização Imunológica , Modelos Animais de Doenças , Método Duplo-Cego , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Lactente , Antagonistas de Leucotrienos/uso terapêutico , Medicina Tradicional Chinesa , Camundongos , Camundongos Nus , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Pomadas , Terapia PUVA , Fotoferese , Fototerapia , Placebos , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia UltravioletaRESUMO
BACKGROUND: Patients with inhalant allergy caused by birch pollen frequently demonstrate immediate symptoms to cross-reactive fruits, vegetables, or both. The nature of late eczematous reactions to pollen related food antigens has not been investigated in detail. OBJECTIVE: The purpose of this study was to find out whether isolated late eczematous reactions to birch pollen-related food antigens can be observed in patients with atopic dermatitis (AD) who are highly sensitized to birch pollen antigens. A possible linkage of such reactions with specific T-cell responses to birch pollen antigens in the blood and lesional skin was examined as well. METHODS: We examined 37 adult patients with AD and hypersensitivity to birch pollen but without any history of immediate responses to food challenges. These patients underwent an elimination diet, including all birch pollen-related food antigens, followed by a double-blind, placebo-controlled, oral provocation. Blood and skin biopsy specimens were taken to examine a birch pollen-specific lymphocyte response. RESULTS: Seventeen patients reacted with a deterioration of AD symptoms. Food- or birch pollen-specific IgE did not differentiate these patients from nonreactive patients. A significantly higher increase in the proportion of blood lymphocytes expressing the cutaneous lymphocyte antigen on incubation with birch pollen antigens was found in cells from reactive compared with nonreactive patients. The proliferative response of skin-derived T-cell lines from reactive patients to birch pollen extract or Bet v 1 was significantly higher than that of nonreactive patients. An enrichment of more than 25% of T-lymphocyte subpopulations defined by T-cell receptor-Vbeta elements was detected in the majority of such antigen-stimulated T-cell lines from responsive patients. A higher frequency of birch pollen-reactive T cells was calculated from limiting-dilution assays, and a higher rate of birch pollen-specific T-cell clones was generated from cultures with skin-derived T cells from reactive patients. CONCLUSION: Our results show, for the first time, that a subpopulation of patients with hypersensitivity to birch pollen and AD reacts with worsening of eczema after oral challenge with birch pollen-related foods and that a birch pollen-specific T-cell response can be found in the lesional skin of these patients.
Assuntos
Antígenos/imunologia , Dermatite Atópica/imunologia , Hipersensibilidade Alimentar/imunologia , Proteínas de Plantas/imunologia , Pele/patologia , Linfócitos T/imunologia , Administração Oral , Adolescente , Adulto , Alérgenos/administração & dosagem , Alérgenos/imunologia , Antígenos de Plantas , Dermatite Atópica/sangue , Método Duplo-Cego , Hipersensibilidade Alimentar/complicações , Humanos , Imunidade Celular , Pessoa de Meia-Idade , Placebos , Pólen/imunologia , Resultado do TratamentoAssuntos
Alérgenos/efeitos adversos , Proteínas Contráteis , Dermatite Atópica/etiologia , Hipersensibilidade Alimentar/complicações , Pólen/efeitos adversos , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Alérgenos/imunologia , Alérgenos/farmacologia , Antígenos de Plantas , Apiaceae/imunologia , Reações Cruzadas , Daucus carota/imunologia , Dermatite Atópica/dietoterapia , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Método Duplo-Cego , Feminino , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/dietoterapia , Hipersensibilidade Alimentar/imunologia , Humanos , Ativação Linfocitária , Masculino , Proteínas dos Microfilamentos/imunologia , Proteínas dos Microfilamentos/farmacologia , Pessoa de Meia-Idade , Nozes/imunologia , Proteínas de Plantas/imunologia , Proteínas de Plantas/farmacologia , Profilinas , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/farmacologia , Rosales/imunologia , Pele/imunologia , Pele/patologia , ÁrvoresRESUMO
BACKGROUND: The results of an open, single-center study suggested that phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective for acute, severe exacerbations of atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute, severe AD in a randomized multicenter trial in direct comparison with topical glucocorticoid therapy. METHODS: Patients were treated with high-dose UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1 x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema dose-dependent; n = 16). RESULTS: With a clinical scoring system, significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p < 0.002) therapy. Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone, but not UVA-UVB therapy. CONCLUSION: This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD.
Assuntos
Dermatite Atópica/radioterapia , Terapia Ultravioleta/métodos , Administração Tópica , Adulto , Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Feminino , Fluocortolona/uso terapêutico , Glucocorticoides , Humanos , Masculino , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Clinical observations suggest that psychological stress can induce exacerbation of psoriasis. It is hypothesized that these stress effects on the course and outcome of psoriasis are caused by neuroendocrine modulation of immune functions. Therefore we investigated the cardiovascular, endocrine and immunological response to a laboratory stressor in psoriasis patients and healthy controls. METHODS: Untreated (n = 7) and PUVA-treated (n = 4) psoriatics and healthy controls (n = 7) were exposed to a brief laboratory stressor (public speaking and mental arithmetic). Heart rate and blood pressure, catecholamine, cortisol, and DHEA plasma concentration, as well as distribution of T and NK lymphocytes were analyzed before, immediately after and 1 h after stress exposure. RESULTS: Heart rate and blood pressure increased in all three groups during stress exposure with the most pronounced changes in PUVA-treated patients. Psoriasis patients displayed higher adrenaline values but diminished cortisol and DHEA plasma concentrations compared to controls. NK cell numbers (CD16+, CD56+), but not T lymphocyte subsets, increased immediately after stress exposure in untreated patients and controls. This effect was significantly diminished in PUVA-treated patients. CONCLUSIONS: The data of this pilot study indicate an enhanced stress-induced autonomic response and diminished pituitary-adrenal activity in psoriasis patients. PUVA treatment seems to interfere with the cardiovascular and NK cell response to acute psychological stress. Future studies will analyze the stress-induced neuroimmunological mechanisms in psoriatics in more detail.
Assuntos
Sistemas Neurossecretores/fisiologia , Terapia PUVA , Sistema Hipófise-Suprarrenal/imunologia , Psoríase/imunologia , Psoríase/psicologia , Estresse Psicológico , Adulto , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Imunidade Celular , Células Matadoras Naturais , Subpopulações de Linfócitos , Masculino , Projetos Piloto , Psoríase/terapiaRESUMO
Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.
Assuntos
Apoptose/imunologia , Apoptose/efeitos da radiação , Oxigênio/farmacologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/efeitos da radiação , Terapia Ultravioleta , Anticorpos Bloqueadores/farmacologia , Apoptose/efeitos dos fármacos , Dermatite Atópica/imunologia , Dermatite Atópica/radioterapia , Deutério/farmacologia , Proteína Ligante Fas , Humanos , Ligantes , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/efeitos da radiação , Naftóis/farmacologia , Oxigênio Singlete , Azida Sódica/farmacologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Receptor fas/imunologia , Receptor fas/metabolismoRESUMO
BACKGROUND: Short-term immunotherapy (STI) can be beneficial for patients who are noncompliant with long-term specific immunotherapy. OBJECTIVE: The efficacy and tolerance of STI with seven preseasonal injections of molecular standardized allergens from grass and rye pollen has been investigated in a double-blind, placebo-controlled multicenter study with 87 patients at 12 German University hospitals. METHODS: Symptoms of the eyes, nose, and bronchi and use of symptomatic drugs were documented daily in diaries by patients with allergic rhinitis to grass and/or rye pollen and without bronchial asthma. Patients were monitored by skin prick test titration and measurement of levels of specific IgE and IgG4. RESULTS: The median nasal score for the 10 weeks with the strongest symptoms during the grass pollen season was significantly lower (p = 0.014) with 35.0 for STI (n = 41) versus 69.0 for placebo (n = 40); the overall symptom score was 54.0 for STI versus 97.5 for placebo (p = 0.020). Only STI-treated patients exposed to less than 40 pollen grains per cubic meter per week showed a significantly lower nasal symptom score of 39.0 versus 75.0 for placebo (p = 0.006); these patients also had fewer nasal symptoms and less use of topical nasal drugs (p < 0.001). The threshold dose in skin prick tests was significantly higher, being 9.06 histamine equivalent for skin prick test (HEP) for STI-treated patients who received the maximum dose (n = 22) versus 4.33 HEP for placebo (p = 0.005). Specific IgE levels were significantly higher, being 55.9 SU/ml for STI versus 39.2 SU/ml for placebo after seven injections (p = 0.006) and level of specific IgG4 was 5.36% for STI versus 1.28% for placebo (p < 0.001). No severe systemic reactions were observed. CONCLUSION: STI with seven preseasonal injections with molecular standardized allergens is effective and well tolerated.
Assuntos
Alérgenos/uso terapêutico , Dessensibilização Imunológica , Poaceae/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/etiologia , Rinite Alérgica Sazonal/terapia , Adolescente , Adulto , Alérgenos/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/normas , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Feminino , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lolium/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Padrões de Referência , Rinite Alérgica Sazonal/tratamento farmacológico , Fatores de TempoRESUMO
Atopic dermatitis (AD) is considered a T-cell mediated disease. Activated T-cells, mainly of the CD4-subtype, are abundantly present in lesional AD skin. Although not many intact eosinophils are present, deposits of eosinophil derived major-basic-protein (MBP) and eosinophil-cationic-protein (ECP) suggest eosinophil involvement. After patch testing AD patients with aeroallergens, an eczematous reaction develops after 24-48 hr at the site of application. This patch test reaction shows macroscopic resemblance to lesional AD skin and does not take place in normal individuals, asthma and allergic rhinitis patients. Lymphocytes together with eosinophils infiltrate into the dermis 2-6 hr after allergen application. Twenty-four to forty-eight hours after patch testing, eosinophils are in an activated state since they release ECP (being EG2-positive). At this point in time eosinophils have also infiltrated the epidermis. Here they are EG2-negative. Forty-eight to seventy-two hours after patch testing the eczematous reaction decreases. This coincides with disappearance of eosinophils from both the dermis and the epidermis; then, a dendritic staining pattern can be observed in the epidermis with anti-eosinophil peroxidase. Thus, eosinophils infiltrate the dermis and epidermis after patch testing AD patients with aeroallergens and release part of their granular constituents. Recent in vitro investigations revealed that eosinophils from the circulation of AD patients react more powerfully in in vitro test systems such as chemiluminescence, chemotaxis and endothelial adherence and transmigration. It is very likely that this activated (= primed) state is caused by the influence of lymphocyte-derived cytokines like IL-3, IL-5 and GM-CSF, since activated lymphocytes in the circulation (and tissue) may release these cytokines. The primed state of the eosinophils may facilitate tissue infiltration. The subsequent activation of eosinophils within the tissue leading to mediator release and the function of these mediators need to be further elucidated. The close similarity between the cellular events after a patch test reaction to aeroallergens in AD patients and those present in lesional AD skin suggests that the patch test reaction may be a helpful in vivo model to study the pathogenesis of AD. The prominent involvement of lymphocytes and eosinophils in this reaction also suggests some similarity with late phase reactions (LPR) observed in the skin after intracutaneous allergen challenge.